The intent of this research proposal is to continue studies into two aspects of the pathogenesis of glomerulonephritis: 1) the way in which immune complexes come to be localized within the glomerulus, and 2) the mechanisms of glomerular inflammation and damage in "proliferative" glomerulonephritis. The first part of this proposal is directed at studying the size of immune aggregates that can become trapped in the glomerulus, and the conditions under which such deposition can occur. We propose to complete characterization of a model of acute and reversible increase of glomerular permeability to proteins induced by infusion of hexadimethrine. Using this model and size defined covalently linked oligomers of IgG, we propose to study the effects of immune aggregate size and glomerular permeability on glomerular immune aggregate deposition. The results will be correlated with the detectability of these aggregates in currently used assays for immune complexes. The second part of the proposal is concerned with mechanisms of glomerular inflammation and damage in "proliferative" immune complex glomerulonephritis. Recently, we have shown that glomerular hypercellularity in acute experimental serum sickness nephritis is the result principally of monocyte infiltration. We propose to define further the role of the monocyte a) by studying the effects of monocyte depletion in acute serum sickness in rabbits and b) by studying the role of the monocyte, using histochemical stains, in chronic experimental and human immune complex disease. Finally, using a model of passively deposited glomerular immune aggregates, we intend to study directly, by passive serum and lymphocyte transfers, the relative roles and interactions of humoral and cellular immunity in glomerular inflammation in immune complex associated nephritis.